Publications by authors named "Ken Okamura"

61 Publications

AIM2 regulates anti-tumor immunity and is a viable therapeutic target for melanoma.

J Exp Med 2021 Sep 29;218(9). Epub 2021 Jul 29.

Department of Dermatology, University of Massachusetts Medical School, Worcester, MA.

The STING and absent in melanoma 2 (AIM2) pathways are activated by the presence of cytosolic DNA, and STING agonists enhance immunotherapeutic responses. Here, we show that dendritic cell (DC) expression of AIM2 within human melanoma correlates with poor prognosis and, in contrast to STING, AIM2 exerts an immunosuppressive effect within the melanoma microenvironment. Vaccination with AIM2-deficient DCs improves the efficacy of both adoptive T cell therapy and anti-PD-1 immunotherapy for "cold tumors," which exhibit poor therapeutic responses. This effect did not depend on prolonged survival of vaccinated DCs, but on tumor-derived DNA that activates STING-dependent type I IFN secretion and subsequent production of CXCL10 to recruit CD8+ T cells. Additionally, loss of AIM2-dependent IL-1β and IL-18 processing enhanced the treatment response further by limiting the recruitment of regulatory T cells. Finally, AIM2 siRNA-treated mouse DCs in vivo and human DCs in vitro enhanced similar anti-tumor immune responses. Thus, targeting AIM2 in tumor-infiltrating DCs is a promising new treatment strategy for melanoma.
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http://dx.doi.org/10.1084/jem.20200962DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8329870PMC
September 2021

Gaining Insight into Vitiligo Genetics through the Lens of a Large Epidemiologic Study.

J Invest Dermatol 2021 Apr;141(4):718-721

Department of Dermatology, University of Massachusetts Medical School, Worcester, Massachusetts, USA. Electronic address:

Several epidemiologic studies and GWASs have implicated genetic factors in the pathogenesis of vitiligo. The report by Kim et al. (2020) describes a prospective cohort study from Korea that has the greatest statistical power to date in addressing the epidemiology of vitiligo inheritance. The authors reported the incidence risk ratios in individuals whose first-degree relatives or spouses are affected, providing clear evidence that both genetic and nongenetic factors influence the pathogenesis of vitiligo.
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http://dx.doi.org/10.1016/j.jid.2020.10.005DOI Listing
April 2021

Hemodilution Impacts Assessment of Thyroid Status before and after Hemodialysis in Patients with End-Stage Renal Disease.

Am J Nephrol 2021 Feb 1;51(12):988-994. Epub 2021 Feb 1.

Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

Background: To elucidate the role of hemodilution in the alteration of thyroid hormone levels in end-stage renal disease (ESRD), we compared thyroid function before and after hemodialysis (HD).

Methods: Twenty-three male ESRD patients (age <65 years) with either chronic glomerulonephritis (CGN) or diabetic nephropathy (DN), who were enrolled between June 2019 and August 2019, were included in the study. The free thyroxine (fT4), free tri-iodothyronine (fT3), and thyroid-stimulating hormone (TSH), thyroxine-binding globulin (TBG), and thyroglobulin (Tg), measured before and after HD in 12 patients with CGN (48.7 ± 11.8 years [mean ± standard deviation]) and 11 patients with DN (57.6 ± 6.5 years), were compared with 45 healthy controls (52.5 ± 11.9 years).

Results: The fT4, fT3, and TBG were significantly low before HD and increased in parallel with an increase in hematocrit and albumin after HD in both ESRD subgroups. The TSH was high before HD and decreased significantly after HD, while Tg remained almost unchanged. In DN, the fT4 levels were nearly identical, while fT3 was lower with slightly higher TSH, compared with CGN. The TSH/fT4 ratios before HD were significantly higher in both subgroups, and the fT3/fT4 ratios after HD were significantly lower in DN than the control.

Conclusions: Our findings suggest that the low fT4 and fT3 levels found in ESRD are due to hemodilution before HD, resulting in a slightly higher TSH level but almost unchanged Tg level, and that DN is associated with decreased T4-to-T3 conversion.
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http://dx.doi.org/10.1159/000512968DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7949231PMC
February 2021

Report of two Japanese patients with piebaldism including a novel mutation in KIT.

J Dermatol 2021 Feb 6;48(2):e94-e95. Epub 2020 Nov 6.

Department of Dermatology, Faculty of Medicine, Yamagata University, Yamagata, Japan.

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http://dx.doi.org/10.1111/1346-8138.15684DOI Listing
February 2021

Five novel mutations in SASH1 contribute to lentiginous phenotypes in Japanese families.

Pigment Cell Melanoma Res 2021 03 8;34(2):174-178. Epub 2020 Oct 8.

Department of Dermatology, Faculty of Medicine, Yamagata University, Yamagata, Japan.

SASH1 has been reported as a causal gene of lentiginous phenotypes with and without heredity, including an autosomal dominant type characterized by lentigines predominantly on sun-exposed areas such as the face and limbs. Recently, cases of dyschromatosis with SASH1 mutations have been reported worldwide; however, only one case has been reported from Japan. Here, we analyzed six Japanese patients who characteristically showed many lentigines on sun-exposed areas, using next-generation sequencing. We identified five novel heterozygous mutations in SASH1 (p.I586M, p.S531Y, p.R644W, p.T525R, and p.S516I) in our patients and their families. The p.R644W substitution identified in two unrelated families was the first mutation located in the sterile alpha motif 1 (SAM1) domain. The degree and location of the lentigines were variable across individuals, even if they shared the same SASH1 mutation. All mutations were predicted to be deleterious by six different algorithms used to evaluate the functional impact of a variation. In addition, immunohistopathological findings and RNA sequencing results suggested that SASH1 mutations were associated with an increase in the number of melanocytes, acceleration of melanogenesis, and upregulated hair keratin expression.
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http://dx.doi.org/10.1111/pcmr.12930DOI Listing
March 2021

Current landscape of Oculocutaneous Albinism in Japan.

Pigment Cell Melanoma Res 2021 03 7;34(2):190-203. Epub 2020 Oct 7.

Department of Dermatology, Faculty of Medicine, Yamagata University, Yamagata, Japan.

Oculocutaneous albinism (OCA), which is roughly divided into non-syndromic and syndromic OCA, is a group of autosomal recessive disorders caused by mutations in genes associated with pigmentation. Patients with OCA have hypopigmentation and ocular manifestations such as photophobia, amblyopia, and nystagmus. Hermansky-Pudlak syndrome (HPS), the most common syndromic OCA, is characterized by the additional features of a bleeding tendency and other critical systemic comorbidities such as pulmonary fibrosis and immunodeficiency. NGS-based gene analyses have identified several new causative genes for OCA and have detected rare subtypes of OCA with high accuracy including Japanese patients. In our survey of 190 Japanese OCA patients/families, OCA4 is the most common subtype (25.3%) followed by OCA1 (20.0%), HPS1 (14.7%), and OCA2 (8.4%). Similar to the A481T variant in OCA2, which is associated with a mild form of OCA2 and skin color variation, the c.-492_489delAATG variant located in the promoter region of SLC45A2 has been uniquely identified in Japanese patients with a mild form of OCA4. Further, rare OCA subtypes, including OCA3, HPS2, HPS3, HPS4, HPS5, HPS6, and HPS9, have also been identified in Japanese patients. The clinical characteristics and underlying molecular mechanisms of each subtype of OCA are concisely summarized in this review.
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http://dx.doi.org/10.1111/pcmr.12927DOI Listing
March 2021

Benford's Law and COVID-19 reporting.

Econ Lett 2020 Nov 14;196:109573. Epub 2020 Sep 14.

Saïd Business School, University of Oxford, Park End Street, Oxford, OX1 1HP, United Kingdom.

Trust in the reported data of contagious diseases in real time is important for policy makers. Media and politicians have cast doubt on Chinese reported data on COVID-19 cases. We find Chinese confirmed infections match the distribution expected in Benford's Law and are similar to that seen in the U.S. and Italy. We identify a more likely candidate for problems in the policy making process: Poor multilateral data sharing on testing and sampling.
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http://dx.doi.org/10.1016/j.econlet.2020.109573DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7487520PMC
November 2020

Identification of two novel mutations in a Japanese patient with Hermansky-Pudlak syndrome type 5.

J Dermatol 2020 Nov 2;47(11):e392-e393. Epub 2020 Sep 2.

Department of Dermatology, Yamagata University Faculty of Medicine, Yamagata, Japan.

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http://dx.doi.org/10.1111/1346-8138.15560DOI Listing
November 2020

Expression of discoidin domain receptor 1 and E-cadherin in epidermis affects melanocyte behavior in rhododendrol-induced leukoderma mouse model.

J Dermatol 2020 Nov 8;47(11):1330-1334. Epub 2020 Aug 8.

Department of Dermatology, Yamagata University Faculty of Medicine, Yamagata, Japan.

Vitiligo is a depigmentation disease characterized by gradual loss of melanin and melanocytes from the epidermis. The mechanism of melanocyte loss is not yet known. In this report, we showed that the expression of discoidin domain receptor 1 and E-cadherin, known adhesion molecules, was variable or absent in the epidermis of rhododendrol-induced leukoderma (RDIL) mice during the depigmentation process. Our findings suggest that melanocyte damage by rhododendrol promotes reduction of adhesion molecules not only in melanocytes but also in keratinocytes, and this is associated with the detachment of melanocytes from the basal layer.
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http://dx.doi.org/10.1111/1346-8138.15534DOI Listing
November 2020

Genome-wide association study identifies CDH13 as a susceptibility gene for rhododendrol-induced leukoderma.

Pigment Cell Melanoma Res 2020 11 29;33(6):826-833. Epub 2020 Jun 29.

Department of Dermatology, Faculty of Medicine, Yamagata University, Yamagata, Japan.

Racemic RS-4-(4-hydroxyphenyl)-2-butanol (rhododendrol; trade name: Rhododenol [RD]), which is used in topical skin-lightening cosmetics, was unexpectedly reported in Japan to induce leukoderma or vitiligo called RD-induced leukoderma (RIL) after repeated application. To our knowledge, no studies have investigated chemical-induced vitiligo pathogenesis on a genome-wide scale. Here, we conducted a genome-wide association study (GWAS) for 147 cases and 112 controls. CDH13, encoding a glycosylphosphatidylinositol-anchored protein called T-cadherin (T-cad), was identified as the strongest RIL susceptibility gene. RD sensitivity was remarkably increased by T-cad knockdown in cultured normal human melanocytes. Furthermore, we confirmed tyrosinase upregulation and downregulation of the anti-apoptotic molecules (BCL-2 and BCL-XL), suggesting that T-cad is associated with RD via tyrosinase or apoptotic pathway regulation. Finally, monobenzyl ether of hydroquinone sensitivity also tended to increase with T-cad knockdown, suggesting that the T-cad could be a candidate susceptibility gene for RIL and other chemical-induced vitiligo forms. This is the first GWAS for chemical-induced vitiligo, and it could be a useful model for studying the disease's genetic aspects.
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http://dx.doi.org/10.1111/pcmr.12904DOI Listing
November 2020

Case of phaeohyphomycosis caused by Cladophialophora boppii successfully treated with local hyperthermia and systemic terbinafine.

J Dermatol 2020 Jul 24;47(7):e250-e251. Epub 2020 Apr 24.

Department of Dermatology, Yamagata University Faculty of Medicine, Yamagata, Japan.

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http://dx.doi.org/10.1111/1346-8138.15357DOI Listing
July 2020

Clinical experience of treating Graves' hyperthyroidism complicated with malignancy-The possible role of potassium iodide for avoiding the risk of thionamide-associated neutropenia.

Endocr J 2020 Jul 2;67(7):751-758. Epub 2020 Apr 2.

Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.

The treatment of Graves' hyperthyroidism (GD) complicated with malignancy is challenging, as anti-thyroid thionamide drugs (ATDs) and anti-cancer chemotherapy are both associated with a risk of neutropenia. Treatment with conventional ATDs, radioactive iodine (RAI) or potassium iodide (KI) was attempted in 8 patients with malignancy (34-80 years of age; 2 males and 6 females) in whom GD had been fortuitously diagnosed during a detailed systematic examination. Three patients requiring surgery were initially treated conventionally with methylmercaptoimidazole (MMI), MMI and KI or RAI (group A; one patient each). The patients became euthyroid on days 17-31 and underwent surgery on days 25-47. RAI therapy was administered to one patient after surgery. The patients were then treated with KI during chemotherapy. Five other patients who did not require surgery were initially treated with 100 mg KI monotherapy (group B). The serum free T level declined immediately in all of these patients, and they became euthyroid on days 7-18, remaining almost entirely euthyroid for more than 120 days. Anti-cancer chemotherapy was successfully completed for three of the patients while taking KI, despite the patients experiencing repeated episodes of anti-cancer chemotherapy-induced neutropenia. Our present findings suggest that, in patients with GD and malignancy, MMI + KI or RAI may be required if immediate surgery is scheduled, but KI monotherapy may be worth trying, if anti-cancer chemotherapy is scheduled, thus avoiding the possibility of thionamide-induced neutropenia.
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http://dx.doi.org/10.1507/endocrj.EJ20-0016DOI Listing
July 2020

Novel AP3B1 compound heterozygous mutations in a Japanese patient with Hermansky-Pudlak syndrome type 2.

J Dermatol 2020 Feb 9;47(2):185-189. Epub 2019 Dec 9.

Department of Pediatrics, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.

Hermansky-Pudlak syndrome type 2 (HPS2) is an extremely rare autosomal recessive inherited disease characterized by partial oculocutaneous albinism (OCA), bleeding diathesis due to a storage pool deficiency and immunodeficiency. The disorder is caused by disruption of the adapter protein 3 complex, which is involved in impaired intracellular vesicle transport. Here, we report the first case of a 1-year-old girl with HPS2 in Asia. She had no specific symptoms other than OCA and neutropenia. We analyzed her platelet function using transmission electron microscopy and a platelet aggregation test, cytotoxic degranulation assay of her natural killer (NK) cells and bleeding time, the results of which led to the diagnosis of HPS2. Although her NK-cell cytotoxic degranulation was impaired, she had not developed signs of hemophagocytic lymphohistiocytosis (HLH) or fibrosing lung disease. Molecular genetic analyses showed novel heterozygous mutations (c.188T>A [p.M63K] and c.2546>A [p.L849X]) in AP3B1. When examining patients with OCA, blood tests should be performed to confirm neutrophil count, bleeding time and platelet agglutination. When HPS2 is suspected, detailed immunological tests should be considered, and attention should be paid to HLH and pulmonary lesions immediately and over the long term.
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http://dx.doi.org/10.1111/1346-8138.15177DOI Listing
February 2020

A toddler case of keratosis follicularis squamosa (Dohi) successfully treated with salicylic acid ointment.

Eur J Dermatol 2019 Oct;29(5):544-546

Department of Dermatology, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan.

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http://dx.doi.org/10.1684/ejd.2019.3624DOI Listing
October 2019

NGS-based targeted resequencing identified rare subtypes of albinism: Providing accurate molecular diagnosis for Japanese patients with albinism.

Pigment Cell Melanoma Res 2019 11 9;32(6):848-853. Epub 2019 Jun 9.

Department of Dermatology, Faculty of Medicine, Yamagata University, Yamagata, Japan.

Albinism, which is commonly inherited as an autosomal recessive trait, is characterized by a reduction or absence of melanin in the eyes, skin, and hair. To date, more than 20 causal genes for albinism have been identified; thus, the accurate diagnosis of albinism requires next-generation sequencing (NGS). In this study, we analyzed 46 patients who tested negative for oculocutaneous albinism (OCA)1-4 and Hermansky-Pudlak syndrome (HPS)1 based on conventional analysis, in addition to 28 new Japanese patients, using NGS-based targeted resequencing. We identified a genetic background for albinism in 18 of the 46 patients (39%), who were previously tested negative according to the conventional analysis. In addition, we unveiled a genetic predisposition toward albinism in 23 of the 28 new patients (82%). We identified six patients with rare subtypes of albinism, including HPS3, HPS4, and HPS6, and found 12 novel pathological mutations in albinism-related genes. Furthermore, most patients who were not diagnosed with albinism by the NGS analysis showed mild manifestations of albinism without apparent eye symptoms and harbored only one heterozygous mutation, occasionally in combination with skin-color associated gene variants.
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http://dx.doi.org/10.1111/pcmr.12800DOI Listing
November 2019

Janus kinase inhibitor tofacitinib does not facilitate the repigmentation in mouse model of rhododendrol-induced vitiligo.

J Dermatol 2019 Jun 10;46(6):548-550. Epub 2019 Apr 10.

Department of Dermatology, Yamagata University School of Medicine, Yamagata, Japan.

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http://dx.doi.org/10.1111/1346-8138.14879DOI Listing
June 2019

The long-term follow-up of patients with thionamide-treated Graves' hyperthyroidism.

Endocr J 2019 Jun 28;66(6):535-545. Epub 2019 Mar 28.

Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.

Since there have been few reports on the long-term prognosis of Graves' hyperthyroidism, the prognosis of 549 Graves' hyperthyroidism patients initially treated with thionamide and followed for >8 (range: 8.6-36.4) years was studied, evaluating the change in the TSH binding inhibitor immunoglobulin activity (TBII). The distribution of the time required for the first disappearance of TBII was normal after logarithmic conversion, and the mean ± 2 SD was 1.5 (0.3-8.1) years. TBII became negative once within 5 years in 78.9% of patients. However, TBII re-elevation was observed in 47.8% of this group (fluctuating type). Remission was observed in 88.9% of the non-fluctuating type (smooth remission) and 37.2% of the fluctuating type patients. TBII remained positive for >5 years in 21.1% (smoldering type) of patients, with remission observed in only 19.8% of patients. Final remission was observed in 301 (54.8%) patients; the median time to remission was 6.8 (interquartile range: 4.0-10.9) years. A longer time until normalization of TBII and higher final thyroid weight were associated with a poor prognosis. Spontaneous hypothyroidism was observed in 6.0% of patients, independent of the TBII change. Our findings suggest that remission of Graves' hyperthyroidism mostly occurred after 4-11 years treatment. While predicting the prognosis before therapy was difficult, the clinical course may suggest a better prognosis if TBII disappears within five years without TBII fluctuation or enlargement of the goiter. Patients may safely wait more than five years to undergo ablative therapy if they hope to avoid permanent hypothyroidism.
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http://dx.doi.org/10.1507/endocrj.EJ18-0418DOI Listing
June 2019

Intralymphatic histiocytosis in a patient with lung adenocarcinoma treated with pembrolizumab: a case report.

J Immunother Cancer 2019 02 27;7(1):59. Epub 2019 Feb 27.

Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School, 1-1-5, Sendagi, Bunkyo-ku, Tokyo, 113-8603, Japan.

Background: Pembrolizumab, an anti-programmed cell death-1 protein monoclonal antibody, is effective for patients with advanced non-small-cell lung cancer. However, immune checkpoint inhibitors such as pembrolizumab induce various immune-related adverse events, involving the lung, liver, gastrointestinal, endocrine system, and skin. Intralymphatic histiocytosis (ILH) is a rare, chronic cutaneous disorder with a reactive inflammatory component, which often occurs in patients with rheumatoid arthritis.

Case Presentation: We present a 67-year-old man with lung adenocarcinoma who developed ILH associated with pembrolizumab treatment. He was treated with palliative thoracic radiotherapy for superior vena cava syndrome. Subsequently, he received four cycles of pembrolizumab. Approximately 2.5 months after the initiation of pembrolizumab, he developed erythema on the trunk of his body. Based on findings of skin biopsies, he was diagnosed with pembrolizumab-induced ILH. Moreover, the upregulation of tumor necrosis factor-α was observed during pembrolizumab therapy.

Conclusions: This is the first report of ILH induced by pembrolizumab in a patient with lung adenocarcinoma.
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http://dx.doi.org/10.1186/s40425-019-0534-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6391791PMC
February 2019

Impact of a 4-bp deletion variant (rs984225803) in the promoter region of SLC45A2 on color variation among a Japanese population.

J Dermatol 2019 08 27;46(8):e295-e296. Epub 2019 Feb 27.

Department of Dermatology, Yamagata University Faculty of Medicine, Yamagata, Japan.

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http://dx.doi.org/10.1111/1346-8138.14831DOI Listing
August 2019

Natural course of epidermolysis bullosa simplex with mottled pigmentation in a Japanese family with the p.P25L mutation in KRT5.

J Dermatol 2019 07 28;46(7):e233-e235. Epub 2019 Jan 28.

Department of Dermatology, Yamagata University Faculty of Medicine, Yamagata, Japan.

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http://dx.doi.org/10.1111/1346-8138.14788DOI Listing
July 2019

A 4-bp deletion promoter variant (rs984225803) is associated with mild OCA4 among Japanese patients.

Pigment Cell Melanoma Res 2019 01 31;32(1):79-84. Epub 2018 Jul 31.

Department of Dermatology, Faculty of Medicine, Yamagata University, Yamagata, Japan.

Oculocutaneous albinism (OCA) type 4 is one of the most common types of albinism among Japanese population. In some patients who were clinically diagnosed with OCA, we have found a heterozygous pathological mutation in the coding region of SLC45A2, the gene responsible for OCA4, not leading to a DNA-based diagnosis. In this study, we evaluated pathological variants in the promoter region of SLC45A2 in these patients. The results indicated that the majority of the patients had a 4-bp deletion in the said region (c.-492_489delAATG; GenBank accession number: NM_016180; rs984225803) in the contralateral allele. These patients displayed a mild phenotype, especially regarding eye manifestations. The results of the luciferase reporter assay and electrophoretic mobility shift assay supported the pathological role of the variant. In addition, four of 220 alleles in Japanese normal control subjects also showed the deletion variant, indicating that this variant could possibly be a skin color-associated variant.
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http://dx.doi.org/10.1111/pcmr.12727DOI Listing
January 2019

Case of anti-p200 pemphigoid accompanying uterine malignancy.

J Dermatol 2018 Dec 15;45(12):e341-e342. Epub 2018 May 15.

Department of Dermatology, Faculty of Medicine, Yamagata University, Yamagata, Japan.

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http://dx.doi.org/10.1111/1346-8138.14473DOI Listing
December 2018

Metyrapone-responsive ectopic ACTH-secreting pheochromocytoma with a vicious cycle via a glucocorticoid-driven positive-feedback mechanism.

Endocr J 2018 Jul 15;65(7):755-767. Epub 2018 May 15.

Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

In ectopic ACTH-secreting pheochromocytoma, combined ACTH-driven hypercortisolemia and hypercatecholaminemia are serious conditions, which can be fatal if not diagnosed and managed appropriately, especially when glucocorticoid-driven positive feedback is suggested with a high ACTH/cortisol ratio. A 46-year-old man presented with headache, rapid weight loss, hyperhidrosis, severe hypertension and hyperglycemia without typical Cushingoid appearance. Endocrinological examinations demonstrated elevated plasma and urine catecholamines, serum cortisol and plasma ACTH. Moreover, his ACTH/cortisol ratio and catecholamine levels were extremely high, suggesting catecholamine-dominant ACTH-secreting pheochromocytoma. Computed tomography revealed a large right adrenal tumor. F-FDG positron emission tomography showed uptake in the area of the adrenal tumor, while I-metaiodobenzylguanidine scintigraphy showed no accumulation. His plasma ACTH level paradoxically became elevated after a dexamethasone suppression test. After metyrapone administration, not only serum cortisol but also plasma ACTH levels were exponentially decreased almost in parallel, suggesting a glucocorticoid-driven positive-feedback regulation in this rapidly exacerbated ectopic ACTH-producing pheochromocytoma. Interestingly enough, plasma catecholamine levels were also decreased by metyrapone, although they remained extremely high. He became severely dehydrated due to hypoadrenalism requiring hydrocortisone supplementation. His clinical signs and symptoms were improved, and right adrenalectomy was performed uneventfully, resulting in complete remission of pheochromocytoma and Cushing's syndrome. A glucocorticoid-driven positive-feedback regulation in this ectopic ACTH-secreting pheochromocytoma created a vicious cycle with rapid exacerbation of both hypercortisolemia and hypercatecholaminemia with extremely elevated plasma ACTH level. Metyrapone was clinically effective to stop this vicious cycle; nonetheless, great care must be taken to avoid hypoadrenalism especially when hypercatecholaminemia remained.
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http://dx.doi.org/10.1507/endocrj.EJ18-0025DOI Listing
July 2018

Waardenburg syndrome type IIE in a Japanese patient caused by a novel non-frame-shift duplication mutation in the SOX10 gene.

J Dermatol 2018 May 23;45(5):e110-e111. Epub 2017 Nov 23.

Department of Dermatology, Yamagata University Faculty of Medicine, Yamagata, Japan.

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http://dx.doi.org/10.1111/1346-8138.14151DOI Listing
May 2018

Characterization of melanosomes and melanin in Japanese patients with Hermansky-Pudlak syndrome types 1, 4, 6, and 9.

Pigment Cell Melanoma Res 2018 03 2;31(2):267-276. Epub 2017 Nov 2.

Department of Dermatology, Faculty of Medicine, Yamagata University, Yamagata, Japan.

Hermansky-Pudlak syndrome (HPS) is an autosomal recessive disorder characterized by oculocutaneous albinism (OCA), a bleeding tendency, and ceroid deposition. Most of the causative genes for HPS encode subunits of the biogenesis of lysosome-related organelles complex (BLOC). In this study, we identified one patient each with HPS4, HPS6, and HPS9 by whole-exome sequencing. Next, we analyzed hair samples from the three patients and representative patients with HPS1 and controls using electron microscopy and chemical methods. All HPS patients had fewer, smaller, and more immature melanosomes than healthy controls. Further, all patients showed reduced total melanin content and increased levels of benzothiazine-type pheomelanin. The results of this study demonstrate the impact of the dysfunctions of BLOCs on the maturation of melanosomes and melanin levels and composition through analysis of their hair samples.
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http://dx.doi.org/10.1111/pcmr.12662DOI Listing
March 2018

Thyroid function in patients on continuous ambulatory peritoneal dialysis in comparison with chronic kidney disease
.

Clin Nephrol 2018 Mar;89(3):181-186

Background/methods: Thyroid function was evaluated in 14 Japanese patients on continuous ambulatory peritoneal dialysis (CAPD) with end-stage renal disease compared with 11 chronic kidney disease (CKD) stage 1+2 patients (glomerular filtration rate ≥ 60 mL/min/1.73m2).

Results: The serum free triiodothyronine (fT3) (2.2 ± 0.3 pg/mL, p < 0.05) levels were lower, and the rate of low triiodothyronine (T3) syndrome was higher (4 of 13 cases, 30.8%) in the CAPD patients than in the CKD stage 1+2 patients (1 of 10 cases, 10.0%, respectively) or the 57 age-matched healthy controls. The serum thyroglobulin (Tg) levels were significantly higher in the CAPD patients (39.7 (13.4 - 178.0) ng/mL) than in the CKD stage 1+2 patients (9.9 (5.5 - 28.8) ng/mL, p < 0.05). High serum Tg levels (> 30 ng/mL) were observed in 66.7% of the CAPD patients.

Conclusion: The finding from our study suggested the deterioration of thyroid function with higher prevalence of low T3 syndrome in the CAPD patients. Although speculation as to the reasons for this would be unwise at this point, we did note that the serum Tg levels were very high in the CAPD patients.
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http://dx.doi.org/10.5414/CN109228DOI Listing
March 2018

Ultrastructural study of dyschromatosis symmetrica hereditaria with widespread pigmentary eruption.

J Dermatol 2017 Jul 31;44(7):e150-e151. Epub 2017 Mar 31.

Department of Dermatology, Yamagata University Faculty of Medicine, Yamagata, Japan.

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http://dx.doi.org/10.1111/1346-8138.13849DOI Listing
July 2017

The high prevalence of reversible subclinical hypothyroidism with elevated serum thyroglobulin levels in chronic kidney disease patients
.

Clin Nephrol 2017 May;87 (2017)(5):237-244

Background: We examined the thyroid function of non-dialysis-dependent chronic kidney disease (CKD) patients in Japan.

Methods: Serum-free thyroxine, free triiodothyronine, thyroid-stimulating hormone (TSH), and thyroglobulin (Tg) levels were evaluated in 37 CKD patients. CKD was defined as sustained kidney damage for more than 3 months and was classified as CKD 1+2 (n = 11), 3+4 (n = 10), or 5 (n = 16), which were defined by glomerular filtration rates of ≥ 60, 15 - 59, or < 15 mL/min/1.73m2, respectively.

Results: The prevalence of primary hypothyroidism (TSH ≥ 4.83 mU/L) in CKD 1+2, CKD 3+4, and CKD 5 was 9%, 20%, and 56%, respectively (p < 0.05). Unexpectedly, elevated serum Tg levels (> 30 ng/mL), a marker of the reversible recovery of the thyroid function, were found in 67% of the CKD 5 patients (p < 0.05). The serum TSH and Tg levels became lower, without replacement therapy, after the initiation of hemodialysis and iodine restriction, and there was a significant correlation between the serum TSH and Tg levels in the CKD 5 patients (p < 0.05).

Conclusion: The high prevalence of reversible hypothyroidism and the TSH-dependent elevation of the serum Tg levels was suggested in Japanese patients with advanced CKD. The excess ingestion and the impaired urinary excretion of iodine may be responsible for this reversible thyroid dysfunction.
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http://dx.doi.org/10.5414/CN109008DOI Listing
May 2017
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